Abstract
We explored the hypothesis that sorafenib may improve the effect of transarterial chemoembolization (TACE) in patients with recurrent hepatocellular carcinoma (HCC) and that longer sorafenib duration was associated with additional survival benefits. In this retrospective, nested case-controlled study, 1126 cases of unresectable HCC were collected. Patients with unresectable disease treated with TACE+sorafenib (n=245) and TACE alone (n=245) and those with recurrence after surgery treated with TACE+sorafenib (n=127) and TACE alone (n=127) were identified and matched according to sex, age, and lesion size and number. The clinicopathological factors associated with survival were examined by univariate and multivariate analyses. The mean duration of sorafenib treatment was 10.8±10.51 months. Sorafenib significantly increased the median survival time as compared to TACE alone (unresectable HCC: 20.23 vs. 13.97 months, respectively; p=0.013 and recurrent HCC: 30.7 and 18.22 months, respectively; p=0.003). The survival of patients with unresectable HCC was associated with the presence of portal vein tumor thrombus (HR=1.47, p=0.004) and treatment method (TACE+sorafenib combination therapy; HR=0.72, p=0.003). For patients with recurrent HCC, the presence of extrahepatic metastasis (HR=1.71, p=0.012) and treatment method (TACE+sorafenib therapy; HR=0.60, p=0.002) also was associated with survival. For patients treated with TACE+sorafenib, multivariate analysis showed decreased hazard of death with longer duration of sorafenib treatment (HR=0.9, p<0.001). Thus, sorafenib plus TACE may provide survival benefits, which may be related with sorafenib treatment duration, particularly for patients with HCC recurrence. Further clinical studies are required to confirm these results and identify which patients are most likely to benefit from this therapeutic strategy.
Highlights
Liver cancer is the fifth most frequently diagnosed cancer worldwide and the second leading cause of cancerrelated death [1]
We explored the hypothesis that sorafenib may improve the effect of transarterial chemoembolization (TACE) in patients with recurrent hepatocellular carcinoma (HCC) and that longer sorafenib duration was associated with additional survival benefits
We hypothesized that the addition of sorafenib may improve the effect of TACE in patients with recurrent HCC and that longer duration of sorafenib therapy may provide survival benefits
Summary
Liver cancer is the fifth most frequently diagnosed cancer worldwide and the second leading cause of cancerrelated death [1]. A majority of patients with liver cancer are diagnosed with hepatocellular carcinoma (HCC). For many HCC patients, hapatectomy and orthotopic liver transplantation are unsuitable due to the advanced stage at initial diagnosis [2,3]. For patients with unresectable HCC, transarterial chemoembolization (TACE) is the standard therapy. In addition to TACE, sorafenib, a tyrosine kinase inhibitor [4] that suppresses HCC cell proliferation and angiogenesis, is used for patients with advanced HCC [5]. Sorafenib suppression of tumor growth and metastasis by STAT3 inhibition was shown in a rat HCC model [6]
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